Assessment of myocardial perfusion with MRI using a modified dual bolus method.

Quantification of regional myocardial blood flow (rMBF) with first-pass magnetic resonance imaging (FP-MRI) requires two contrast agent injections (dual bolus technique), inducing error in the determined rMBF if the injections differ. We hypothesize that using input and residue curves of the same injection would be more reliable. We aim to introduce and evaluate a novel method to correct the high concentration arterial input function (AIF) for determination of rMBF. Sixteen patients with non-Hodgkin's lymphoma were examined before and after chemotherapy. The input function was solved by correcting initial high concentration AIF using the ratio of low and high contrast AIF areas, normalized by corresponding heart rates (modified dual bolus method). For comparison, the scaled low contrast AIF was used as an input function (dual bolus method). Unidirectional transfer coefficient K(trans) was calculated using both methods. K(trans)-values determined with the dual bolus (0.81 ± 0.32 ml g(-1) min(-1)) and modified dual bolus (0.77 ± 0.42 ml g(-1) min(-1)) methods were in agreement (p = 0.21). Mean K(trans)-values increased from 0.76 ± 0.43 to 0.89 ± 0.55 ml g(-1) min(-1) after chemotherapy (p = 0.17). The modified dual bolus technique agrees with the dual bolus technique (R2 = 0.899) when the low and high contrast injections are similar. However, when this is not the case, the modified dual bolus technique may be more reliable.

Bioimpedance-based measurement method for simultaneous acquisition of respiratory and cardiac gating signals.

Respiratory and cardiac motion artefacts impair the quality and reliability of medical imaging, particularly in nuclear medicine. At worst, the interpretation of distorted images may lead to inadequate or unnecessary treatment. Image artefacts can be minimized by gating the image acquisition according to respiratory phase and cardiac contractions. However, currently there are no clinically established dual-gating methods in nuclear medicine imaging. The aim of this study is to validate a previously determined optimized bioimpedance measurement configuration against traditional respiratory and cardiac measurement systems in 12 volunteers. High agreement and excellent correlations (r = 0.944-0.999) were found between respiratory peak-to-peak amplitudes as well as temporal respiratory and cardiac intervals. Above all, good quality respiratory and cardiac gating signals were obtained from all test subjects with a fairly regular sinus rhythm. Importantly, both signals were acquired simultaneously with a single device. Due to the simplicity of this inexpensive method, the technique has high potential to be adopted for dual-gating in clinical practice in the future.

Effects of fluoxetine treatment on striatal dopamine transporter binding and cerebrospinal fluid insulin-like growth factor-1 in children with autism.

A positive effect of fluoxetine has been shown in some children with autism. The present study was undertaken to correlate striatal dopamine transporter (DAT) binding and cerebrospinal fluid insulin-like growth factor-1 (CSF-IGF-1) with clinical response in autistic children (n=13, age 5-16 years) after a 6-month fluoxetine treatment. Good clinical responders (n=6) had a decrease (p=0.031) in DAT binding as assessed using single-photon emission computed tomography with [123I]-nor-ß-CIT, whereas poor responders had a trend to an increase. An increase in CSF-IGF-1 (p=0.003) was detected after the treatment period, but no correlation between the clinical response and CSF-IGF-1 was found. In conclusion, fluoxetine decreases DAT binding indicating alleviation of the hyperdopaminergic state and increases CSF-IGF-1 concentration, which may also have a neuroprotective effect against dopamine-induced neurotoxicity in autistic children.

Cerebellar apparent diffusion coefficient changes in patients with supratentorial ischemic stroke.

OBJECTIVES: To evaluate apparent diffusion coefficient (ADC) in cerebellar subregions in patients with stroke. MATERIALS AND METHODS: The total counts and ADCs were bilaterally measured on cerebellar white matter, gray matters of medial (G1), intermediate (G2), and lateral zones (G3) on SPECT and ADC maps from 20 patients with supratentorial ischemic stroke within the first 48 h and on day 8 after onset. ADCs were also obtained from 15 age-matched controls. RESULTS: Within 48 h, the ADCs were significantly increased bilaterally in the G3, and tended to be increased bilaterally in the white matter and G1, and contralateral G2 compared with controls. On day 8, the ADCs were significantly increased in all contralateral cerebellar subregions and in ipsilateral G1 and G2, and tended to be increased in ipsilateral G3. The ADC value was significantly higher in contralateral than in ipsilateral white matter on day 8. The interhemispheric asymmetry indices (AIs) of ADC and SPECT were significantly associated with each other in G2 and G3 within 48 h, but not on day 8. The AIs of ADC and SPECT were significantly related to each other in the G3 within 48 h and on day 8. CONCLUSIONS: Supratentorial ischemic stroke may cause mild cerebellar vasogenic edema.

Heterogeneity of cerebral perfusion 1 week after haemorrhage is an independent predictor of clinical outcome in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid haemorrhage (aSAH) can be associated with acute global and regional decrease in cerebral perfusion. Furthermore, cerebral vasospasm may lead to development of delayed ischaemic deficits. The aim of the study was to find out whether cerebral perfusion heterogeneity, an indicator of cerebral microvascular function and autoregulation, measured by single-photon emission tomography (SPET), is able to predict the long-term clinical outcome of aSAH. METHODS: The perfusion SPET data of 55 patients with aSAH were analysed by dividing the brain into 384 regions of interest. Spatial perfusion heterogeneity was assessed by calculating the relative dispersions (RD, coefficient of variation) from the SPETs performed before treatment (RD1) and 1 week after early surgical or endovascular treatment of the ruptured aneurysm (RD2). Both RDs were compared to the clinical outcome (Glasgow Outcome Scale, GOS), neuropsychological test scores and late ischaemic findings in MRI 1 year after SAH. RESULTS: High RD2 (OR 1.96; 95% CI 1.18-3.26; p = 0.009) and poor clinical condition (Hunt and Hess grade) on admission (OR 6.60; 95% CI 1.78-24.52; p = 0.005) proved to be independent predictors of poor or moderate clinical outcome (GOS 1-4). RD2 was higher in patients with ischaemic findings in 12-month MRI than in those without ischaemic findings (p = 0.008). RD2 also correlated with neuropsychological outcome 1 year after aSAH. CONCLUSIONS: Perfusion heterogeneity is an independent predictor of the clinical outcome of aSAH and may thus be a valuable measure in the assessment of the disease.

Brain serotonin reuptake did not change during one year in overtrained athletes.

Brain 5-HT neurotransmission has been described to be down-regulated in depressed people, and also suspected to be changed in overtraining state, the consequence of long-term physical overloading and stress in athletes. We studied brain serotonin (5-HT) transporter binding i.e., 5-HT reuptake with the specific radioligand (123-I-labelled 2beta-carbomethoxy-3beta[4-iodopenyl]-nortropane, Nor-beta-CIT), and with single photon emission tomography (SPET) in severely overtrained athletes and their controls at the baseline and after a one-year recovery period. Twelve overtrained (6 women and 6 men, mean age 27 yrs, range 16 - 39 yrs) and 11 healthy (6 women, 5 men, 26 yrs, 20 - 39 yrs) athletes were examined. Overtrained athletes 1) had suffered from an unexplained decrement in physical performance and fatigue for several weeks to many months and continued to have the same symptoms even after a recovery time of weeks to months, 2) had been examined to be otherwise healthy, and 3) had a suitable training history for overtraining. Nor-beta-CIT SPET was acquired 5 min, and 3, 6, and 24 h after the injection of the radioligand. 5-HT reuptake in ml/ml in midbrain (raphe nuclei) was calculated as (midbrain - cerebellum)/cerebellum. According to two-way analysis of variance, no changes inside the groups or group differences in 5-HT reuptake were found. Male athletes had significantly higher 5-HT reuptake than female athletes at the baseline (p = 0.034). The overtrained athletes were moderately depressed, while their scores in standardized Hamilton and Montgomery-Asberg Depression Rating Scales were 16 +/- 2 (mean +/- SEM, range 8 - 29) and 17 +/- 2 (7 - 28), respectively. In the CA, the scores were 6 +/- 1 (range 2 - 18) and 6 +/- 2 (1 - 19), respectively. 5-HT reuptake did not correlate with the depression scores either in the whole group or in the OA. The finding of the present study does not support the idea of long-term changes in 5-HT neurotransmission in overtraining state, in this case serotonin reuptake in midbrain, the regulating area of brain serotonin neurotransmission. Furthermore, depression of overtrained athletes may be its own variant having no correlation with 5-HT reuptake in midbrain. Sex may have effect on chronic stress response at the brain level in athletes, which may be a confusing factor in the overtraining studies, and has to be taken into consideration in the future.

Quantitative accuracy of serotonergic neurotransmission imaging with high-resolution 123I SPECT.

AIM: Serotonin transporter (SERT) imaging can be used to study the role of regional abnormalities of neurotransmitter release in various mental disorders and to study the mechanism of action of therapeutic drugs or drugs' abuse. We examine the quantitative accuracy and reproducibility that can be achieved with high-resolution SPECT of serotonergic neurotransmission. METHOD: Binding potential (BP) of (123)I labeled tracer specific for midbrain SERT was assessed in 20 healthy persons. The effects of scatter, attenuation, partial volume, misregistration and statistical noise were estimated using phantom and human studies. RESULTS: Without any correction, BP was underestimated by 73%. The partial volume error was the major component in this underestimation whereas the most critical error for the reproducibility was misplacement of region of interest (ROI). CONCLUSION: The proper ROI registration, the use of the multiple head gamma camera with transmission based scatter correction introduce more relevant results. However, due to the small dimensions of the midbrain SERT structures and poor spatial resolution of SPECT, the improvement without the partial volume correction is not great enough to restore the estimate of BP to that of the true one.

Abnormal serotonin reuptake in an overtrained, insomnic and depressed team athlete.

The purpose of this report is to study serotonin reuptake of the brain in a severely overtrained athlete by using single-photon emission computed tomography (SPECT). A 26-year-old team athlete increased his training volume (by 200 %) and intensity markedly in a new high-level team. After two months, he started to feel continuous fatigue. He had tinnitus in his left ear, he felt disturbing palpitation and had pollacisuria. After four months, he started to suffer from insomnia. He still continued to play for another three months, after which he was unable to play. He could only sleep for 3 to 4 hours per night. Only minor abnormalities could be found in extensive physical and laboratory examinations. The athlete had a severe overtraining state. In the brain SPECT scans, using the specific radioligand for serotonin transporter imaging ( (123)I labelled 2beta-carbomethoxy-3beta-[4-iodophenyl]-nortropane), low activity areas were detected in the midbrain, anterior gingulus, and left frontal and temporo-occipital lobes. In a psychiatric examination, the patient was found to have signs of major depression, which he hardly recognized himself. We conclude, that that the severe overtraining state could have been related to decreased serotonin reuptake in the brain and signs of major depression.

Heterogeneity of cerebral blood flow in symptomatic patients undergoing carotid endarterectomy.

There is still controversy concerning which patients with asymptomatic carotid stenosis or symptomatic moderate stenosis are likely to benefit from carotid endarterectomy. The surgical candidates for carotid endarterectomy should have a high risk for stroke, but a low risk for operative complications. Therefore, new effective patient selection strategies, including haemodynamic testing, schemes of risk stratification and pre-operative cardiac testing, are under investigation. To improve haemodynamic assessment of patients with carotid artery stenosis, we evaluated a novel global cerebral blood flow (CBF) heterogeneity index at rest and after acetazolamide injection in patients undergoing carotid endarterectomy. CBF heterogeneity index was measured in 15 patients by using basal and acetazolamide enhanced 99mTc-HMPAO SPET both before and 1 month after surgery. CBF heterogeneity index was calculated as the coefficient of variation of a total of 44 cerebral regions representing mainly both ipsi- and contralateral grey matter. A high linear correlation was observed between CBF heterogeneity index and ipsilateral carotid stenosis degree (r=0.74, P=0.003). Before surgery, CBF heterogeneity index increased significantly after acetazolamide injection when compared to the basal condition (from 7.0+/-1.5 to 8.3+/-1.7%, P=0.008). This response disappeared after carotid endarterectomy. When compared to pure asymmetry of CBF (ipsi/contralateral CBF ratio), the CBF heterogeneity index seemed to reflect, more sensitively, the haemodynamic effects of carotid endarterectomy. The CBF heterogeneity index after acetazolamide injection is a sensitive marker of the haemodynamic consequences of carotid artery stenosis and its operative treatment.

Extrastriatal dopamine D 2/3 receptor density and distribution in drug-naive schizophrenic patients.

Several lines of studies have suggested the importance of cortical dopamine (DA) transmission in the pathophysiology of schizophrenia. The putative alteration of striatal D(2) receptor density in schizophrenia has been studied intensely, although extrastriatal DA activity may be more relevant for behavioral symptoms. The aim of this study was to explore extrastriatal D(2/3) density in drug-naive schizophrenic patients. We studied the extrastriatal D(2/3) receptor binding with a novel high-affinity single-photon emission tomography ligand epidepride in seven drug-naive schizophrenic patients and seven matched controls. The symptoms were rated with Positive and Negative Syndrome Scale for Schizophrenia. The findings indicated an extremely low D(2/3) receptor binding among patients in temporal cortex in both hemispheres when compared with controls (effect size 2.0-2.3), and the D(2/3) levels had negative correlations with general psychopathological (r from -0.86 to -0.90) and negative (r from -0.37 to -0.55) schizophrenic symptoms. These results support the previous hypothesis on dysfunction of mesocortical DA function behind the cognitive and negative symptoms in schizophrenia.

PET imaging using a triple-head gamma camera.

Interest in clinical fluorodeoxyglucose (FDG) imaging with multiple-head gamma cameras is growing. To improve sensitivity, triple-head coincidence imaging has been proposed. We report our initial experiences with a triple-head coincidence gamma camera with 19 mm sodium iodide crystal thickness. Several positron emission tomography-image quality parameters were evaluated using a Carlson and line source phantom. The system sensitivity with two-dimensional axial shields was 830 cps kBq-1 ml-1 and maximum noise equivalent count rate 1900 cps for an 18F-activity of 50 MBq. The imaging resolution was in central axial 7.0 mm and in central transaxial 7.6 mm, respectively. The average scatter fraction in scattered media was 29%. Clinical brain, heart and whole body images studies with [18F]FDG were acquired and they show good correlation with the phantom image quality. As a conclusion, triple-head coincidence gamma camera provides relatively high-count rate imaging with good contrast and resolution.

Could automated template based quantification of benzodiazepine receptors in brain single photon emission tomography with 123I NNC 13-8241 be used to demonstrate neuronal damage in traumatic brain injury?

Automated methods are required for the analysis of brain single photon emission tomography images. We applied an automated method to assess the benzodiazepine receptor distribution in the brain. Images of 19 patients with mild traumatic brain injury who had received I NNC 13-8241 were compared with a mean brain template accumulated from 18 healthy volunteers. To obtain more information, we calculated the neuronal benzodiazepine receptor binding in the brain by using pre-defined anatomical regions and a voxel-by-voxel technique. The group of patients with mild traumatic brain injury differed significantly (P =0.015) from the group of healthy volunteers in the distribution of benzodiazepine receptors. This methodological work suggests that a reference based template and a three-dimensional brain model help in regional analysis and quantification and could be useful in demonstrating permanent neuronal damage after head injury.

Myocardial fatty acid utilisation during exercise induced ischemia in patients with coronary artery disease.

AIM: Reversible or irreversible myocardial damage due to ischemia correlates with altered membrane functions of the cells. To compare myocardial free fatty acid (FFA) metabolism and flow during exercise induced ischemia we studied ten patients with coronary artery disease but without previous myocardial infarction. METHODS: A series of post-exercise single-photon emission computed tomography (SPECT) measurements was performed after injection of 123I labelled heptadecanoic acid (HDA). Myocardial perfusion was estimated from the separately performed exercise-redistribution thallium study. Fatty acid metabolic rate, thallium uptake and washout were calculated for anterior, lateral, posterior and septal segments. RESULTS: The more reduced post-exercise FFA metabolic rate (-63 +/- 18%, mean +/- 1 SD) compared to flow (-36 +/- 16%) was related to the severity of myocardial ischemia and wall motion abnormalities. CONCLUSION: In this small group of patients, the reduced post-exercise FFA metabolic rate tentatively suggests a parsimonious workload of the exercising myocardium by reducing oxygen consumption in patients with coronary artery disease.

Effect of flow and vascular heterogeneity on glucose metabolism in isolated dog hearts.

In non-ischaemic myocardium glucose uptake is assumed to be proportional to blood flow. We investigated the effect of regional vascular heterogeneity on glucose metabolism at various flow rates in the isolated blood-perfused dog hearts. Aortic bolus injections contained an intravascular reference tracer (albumin) and two of three glucoses: L-glucose (an extracellular tracer), D-glucose and 2-deoxy-D-glucose. Flow ranged from 0.5 to 2 4 ml min(-1) g(-1). Vascular heterogeneity was calculated from the albumin outflow dilution curve. A three-region convection-diffusion from the abumin outflow dilution curve. A three-region, convection-diffusion model was fitted to outflow dilution curves to estimate glucose metabolic rate (consumption). The results of 2-deoxy-D-glucose experiments showed that the lumped constant was dependent on flow, glucose metabolic rate was proportional to flow and dependent on the heterogeneity of the myocardial vasculature. The results support the views that without accounting the regional flow heterogeneity, glucose metabolic rate will be underestimated.

Imaging of the endothelial dysfunction in coronary atherosclerosis.

Coronary endothelial dysfunction is characterised by coronary vasoconstrictive responses to endothelium-dependent vasodilators. It is associated with coronary artery disease (CAD) and is considered an early phase of coronary atherosclerosis. Patients with CAD benefit from vigorous risk factor interventions and medical treatment, with a marked decrease in coronary events and an improvement in survival that are not reported following revascularisation procedures. Therefore, early detection of anatomical and functional changes in the coronary vasculature due to atherosclerosis provides the basis for integrated pharmacological, dietary and lifestyle modifications to prevent cardiovascular events and revascularisation procedures. The question arises as to whether these alterations in regional myocardial tone can be detected by any of the current non-invasive methods. Several methods are reviewed. We consider that intracoronary ultrasonography is the most accurate method, but non-invasive positron emission tomography and magnetic resonance imaging technology is of growing importance for identifying endothelial dysfunction of early coronary atherosclerosis.

Quantitation of neuroreceptors: a need for better SPECT imaging.

AIM: Existing methods to determine the binding potential in brain receptor and transporter studies with single-photon emission computed tomography (SPECT) show a marked dependence on the physical performance of the scanner and on the regions of interest (ROIs) drawn. We examined the influence of the physical performance on the binding potential. METHOD: The authors tested three gamma cameras (single-, dual- and triple-head) and two reconstruction techniques (conventional filtered back-projection and iterative reconstruction method) to determine the binding potential in brain receptor studies. Both human and organ-like phantom studies were performed. RESULTS: The binding potential was completely dependent on the imaging resolution, on the reconstruction technique used and on the ROIs drawn. The results of the phantom study revealed that the striatum-to-cerebellum ratio was only 37% of the actual one for the single-head, 63% for the dual-head and 72% for the triple-head gamma camera. CONCLUSION: The multiple head gamma camera with fan-beam collimators and iterative reconstruction with the attenuation based scatter correction is an imaging system of choice which introduces clinically more relevant images and is able to distinguish smaller differences in radioactivity at early stage of disease. However, for quantitative purposes the improvement without the use of the recovery coefficient is not great enough to restore the binding potentials to those of the true ones.

SPECT and neuropsychological performance in severe depression treated with ECT.

BACKGROUND: In severe depression, studies of regional cerebral blood flow (rCBF) by SPECT have not produced uniform results. The association between changes in SPECT and electroconvulsive therapy (ECT) has shown somewhat conflicting data. No data are available on benzodiazepine receptor function SPECT studies in ECT. METHODS: Twenty drug-resistant adult inpatients fulfilling the DSM-IIIR criteria for major depression were studied by SPECT (rCBF by relative ECD uptake in all, and benzodiazepine receptor function by iomazenil uptake in five subjects) before and 1 week after clinically successful bitemporal ECT. Clinical and neuropsychological test scores were used as references for the possible changes in SPECT. RESULTS: An increased perfusion after ECT was observed in right temporal and bilateral parietal cortices, whereas no reductions in relative ECD uptake were seen after ECT. Iomazenil-SPECT revealed a highly significant increase in the benzodiazepine receptor uptake in all studied cortical regions except temporal cortices. CONCLUSIONS: Clinically successful ECT was associated with changes in vascular perfusion and GABAergic neurotransmission, providing new evidence for the mechanism of action of ECT and for the neurobiology of severe drug-resistant depression.